Platelets play a critical role in hemostasis. A deficiency of platelets (thrombocytopenia) or dysfunction of platelets present at normal levels results in longer-than-normal bleeding time and other disorders. Thrombocytopenia is currently treated with platelet concentrates obtained from healthy donors (Rintels el al., 1994, Transfusion Med. 8:1131). Such treatment has severe drawbacks, however, including (i) the potential transmission of infectious agents, including bacterial and viral agents, (ii) the short shelf-life of donor platelets and the requirement for specialized equipment and methods for handling and storage of platelets, and (iii) a high incidence of alloimmunization. There is, therefore, an urgent need for a platelet substitute that is both efficacious and safe and can be given to patients of different blood types without major transfusion incompatibility.
Physicians and scientists have long sought a source of artificial platelets. As one example, investigators have attached fibrinogen to erythrocytes (Agam et al., 1992, Euro J Clin Invest 22:105; Beer et al., 1992, Blood 79:117; Collar et al., 1992, J Clin. Invest. 89:546). However, the erythrocyte-based system suffers from i) the difficulty of attaching fibrinogen to large numbers of erythrocytes, ii) the requirement for cross-matching with patients, iii) the inherent short storage life and instability of the treated erythrocytes, iv) the potential of transmission of infectious agents.
Other approaches to replace the need of platelet infusions involve the use of lyophilized human platelets, fibrinogen attached to platelet membrane microvesicles, and other attempts at making artificial platelets. However, these products typically have a short in vivo half life or are not efficacious in vivo.
There is, therefore, a need for a platelet substitute that is convenient and effective.